Human 4-1BB receptor splicing variant

• US 5,874,240 A
• Filed: 03/13/1997
• Issued: 02/23/1999
• Est. Priority Date: 03/15/1996
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Yu, Guo-Liang, Ni, Jian, Dillon, Patrick J., Gentz, Reiner
• Primary Examiner(s): Spector, Lorraine
• Assistant Examiner(s): Kaufman, Claire M.
• Application Number:
  US08/816,605
• Time in Patent Office: 712 Days
• Field of Search: 536/23.5, 536/23.1, 530/350, 530/395, 435/69.1, 435/320.1, 435/325, 435/252.3, 435/254.11, 514/12, 514/2
• US Class Current: 435/69.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/715 for cytokines; for lymphokines; for interferons
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to h4-1BBSV receptor polypeptides, polynucleotides encoding the polypeptides, methods for producing the polypeptides, in particular by expressing the polynucleotides, and agonists and antagonists of the polypeptides. The invention further relates to methods for utilizing such polynucleotides, polypeptides, agonists and antagonists for applications, which relate, in part, to research, diagnostic and clinical arts.

Claims

1. An isolated nucleic acid comprising a member selected from the group consisting of:

(a) a polynucleotide encoding amino acids -18 to 201 of SEQ ID NO;

2;

(b) a polynucleotide encoding amino acids -17 to 201 of SEQ ID NO;

2;

(c) a polynucleotide encoding amino acids 1 to 201 of SEQ ID NO;

2;

(d) a polynucleotide encoding amino acids 1 to 132 of SEQ ID NO;

2; and

(e) a polynucleotide complementary to the polynucleotide of (a), (b), (c), or (d).

2. The isolated polynucleotide of claim 1 wherein said member is (a).

3. The isolated polynucleotide of claim 1 wherein said member is (b).

4. The isolated polynucleotide of claim 1 wherein said member is (c).

5. The isolated polynucleotide of claim 1 wherein said member is (d).

6. The isolated polynucleotide of claim 1 wherein the isolated polynucleotide is RNA.

7. A method of making a recombinant vector comprising inserting the isolated polynucleotide of claim 1 into a vector, wherein said polynucleotide is DNA.

8. A recombinant vector comprising the isolated polynucleotide of claim 1, wherein said polynucleotide is DNA.

9. A recombinant host cell comprising the vector of claim 8 comprising said isolated polynucleotide.

10. The isolated polynucleotide of claim 5 comprising the nucleotides 178 to 573 of SEQ ID NO:

1.

11. The isolated polynucleotide of claim 5 comprising the nucleotides 1 to 946 of SEQ ID NO:

1.

12. The isolated polynucleotide of claim 2 comprising the nucleotides 124 to 780 of SEQ ID NO:

1.

13. An expression vector comprising the nucleic acid of claim 1 in operative association with a nucleotide regulatory sequence that controls the expression of the nucleotide sequence in a host.

14. An isolated nucleic acid comprising a polynucleotide selected from the group consisting of:

(a) a polynucleotide encoding the full-length polypeptide encoded by the human cDNA contained in ATCC Deposit No. 97462;

(b) a polynucleotide encoding the full-length polypeptide encoded by the human cDNA contained in ATCC Deposit No. 97462, excepting the N-terminal methionine;

(c) a polynucleotide encoding a mature polypeptide encoded by the human cDNA contained in ATCC Deposit No. 97462; and

(d) a polynucleotide complementary to the polynucleotide of (a), (b) or (c).

15. The isolated polynucleotide of claim 14 wherein said member is (b).

16. The isolated polynucleotide of claim 14 wherein said member is (c).

17. The isolated polynucleotide of claim 14 wherein said member is DNA.

18. A method of making a recombinant vector comprising inserting the isolated polynucleotide of claim 14 into a vector, wherein said polynucleotide is DNA.

19. A recombinant vector comprising the isolated polynucleotide of claim 14 wherein said polynucleotide is DNA.

20. A recombinant host cell comprising the vector of claim 19 comprising said isolated polynucleotide.

21. An isolated polypeptide comprising a polypeptide member selected from the group consisting of:

(a) amino acids -18 to 201 in SEQ ID NO;

2;

(b) amino acids -17 to 201 in SEQ ID NO;

2;

(c) amino acids 1 to 201 in SEQ ID NO;

2; and

(d) amino acids 1 to 132 in SEQ ID NO;

2.

22. The isolated polypeptide of claim 21 wherein said member is (c).

23. The isolated polypeptide of claim 21 wherein said member is (d).

24. A composition comprising a polypeptide of claim 21 and a pharmaceutically acceptable carrier.

25. An isolated polypeptide comprising a polypeptide member selected from the group consisting of:

(a) the full-length polypeptide encoded by the human cDNA clone contained in ATCC Deposit No. 97462;

(b) the full-length polypeptide encoded by the human cDNA clone contained in ATCC Deposit No. 97462 excepting the N-terminal methionine; and

(c) the mature polypeptide encoded by the human cDNA clone contained in ATCC Deposit No. 97462.

26. The isolated polypeptide of claim 25 wherein said member is (b).

27. The isolated polypeptide of claim 25 wherein said member is (c).

28. A composition comprising a polypeptide of claim 25 and a pharmaceutically acceptable carrier.

29. An isolated deletion variant of human 4-1BB receptor having the sequence of SEQ ID NO:

9 from which amino acid residues 34-69 have been deleted, and optionally comprising an alteration selected from the group consisting of;

a) substitution or deletion of an additional 1-10 amino acid residues of SEQ ID NO;

9, and

b) insertion of 1-10 amino acid residues in a region other than the region consisting of amino acid residues 34-69 of SEQ ID NO;

9.

31. A composition comprising a deletion variant of claim 29 or an extracellular domain of claim 30 and a pharmaceutically acceptable carrier.

30. An isolated extracellular domain of a deletion variant of human 4-1BB receptor having the sequence of SEQ ID NO:

9 from of amino acids 19-205 from which amino acid residues 34-69 have been deleted, and optionally comprising an alteration selected from the group consisting of;

a) substitution or deletion of an additional 1-10 amino acid residues of SEQ ID NO;

9, and

b) insertion of 1-10 amino acid residues in a region other than the region consisting of amino acid residues 34-69 of SEQ ID NO;

9.

32. An isolated nucleic acid comprising a polynucleotide which encodes a deletion variant of human 4-1BB receptor having the sequence of SEQ ID NO:

9 from which amino acid residues 34-69 have been deleted, and optionally comprising an alteration selected from the group consisting of;

a) substitution or deletion of an additional 1-10 amino acid residues of SEQ ID NO;

9, and

b) insertion of 1-10 amino acid residues in a region other than the region consisting of amino acid residues 34-69 of SEQ ID NO;

9.

34. A method of making a recombinant vector comprising inserting the isolated nucleic acid of claim 32 or 33 into a vector, wherein said nucleic acid is DNA.

35. A recombinant vector comprising the isolated nucleic acid of claim 32 or 33, wherein said nucleic acid is DNA.

36. A recombinant host cell comprising the vector of claim 35 comprising said isolated nucleic acid.

37. An expression vector comprising the nucleic acid of claim 32 or 33 in operative association with a nucleotide regulatory sequence that controls the expression of the nucleotide sequence in a host.

33. An isolated nucleic acid comprising a polynucleotide which encodes the extracellular domain of a deletion variant of human 4-1BB receptor having the sequence of SEQ ID NO:

9 from of amino acids 19-205 from which amino acid residues 34-69 have been deleted, and optionally comprising an alteration selected from the group consisting of;

a) substitution or deletion of an additional 1-10 amino acid residues of SEQ ID NO;

9, and

b) insertion of 1-10 amino acid residues in a region other than the region consisting of amino acid residues 34-69 of SEQ ID NO;

9.